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Biomedical subjects

N R Saunders

Publications and source records attributed to N R Saunders.

At least 145 records · Page 8Linked to original sources

The Celestin tube in the palliation of carcinoma of the oesophagus and cardia.

A series of 105 patients with dysphagia due to inoperable carcinoma of the oesophagus or cardia of the stomach, and 11 patients with dysphagia secondary to malignant medistinal nodes, was treated by intubation with a Celestin tube. The hospital mortality was high but 81 patients left hospital and 29 were still alive at 6 months. The prognosis for those with dysphagia due to malignant posterior mediastinal nodes was very poor, with no survivors at 6 months. Oesophageal perforation was a serious operative complication, with a hospital mortality of 83 per cent. Chest and wound infections were the most common postoperative complications occurring in 28 and 20 per cent of the patients, respectively. The restoration of swallowing was satisfactory in the majority of survivors although readmission with a blocked or displaced tube was not uncommon.

Adult↗

Double replica technique applied to choroid plexus from early foetal sheep: completeness and complexity of tight junctions.

Choroid plexuses from early and late sheep foetuses were examined by an improved freeze-fracture technique and the use of double-replicas to define the structure of the tight junction network of the epithelial cells. 'Complex' strands which consist of two normal parallel strands separated by a single row of pits or particles are defined and demonstrated in complementary faces. Since this strand variety was encountered in the same proportion in the different development stages investigated, it could not be correlated with changes in permeability. It is more likely that the 'complex' strands are associated with the transfer of gap junction particles within the membrane. The question of the significance of discontinuities in P face ridges was also resolved by the double replica technique: the few discontinuities which were observed could be accounted for by particles in the complementary E faces. Furthermore, approximately the same number of such junction displacements was found in early and late stages which makes it unlikely that this phenomenon could contribute to changes in permeability. Thus it has not been possible so far to relate any structural feature of the tight junction network in developing choroid plexus epithelial cells with the reported changes in permeability of the blood-C.S.F. barrier.

Animals↗

Immunohistochemical evidence for an intracellular localization of plasma proteins in human foetal choroid plexus and brain.

The intracellular distribution of plasma proteins in human foetal choroid plexus and brain was investigated by immunohistochemistry. Small groups of cells or single scattered cells in the epithelial layer of the choroid plexus exhibited positive staining for alpha-fetoprotein, albumin and transferrin, whereas prealbumin was found in the majority of the epithelial cells. Numerous nerve cells in the cerebral wall and in various brain stem nuclei were positively stained for alpha-fetoprotein, albumin and prealbumin. All appropriate controls were negative. The presence of plasma proteins within choroid plexus epithelial cells suggest that these proteins are transported from blood to CSF by a transcellular route across the choroid plexus epithelium. The intracellular distribution of plasma proteins in developing neurons may indicate that these proteins play some important role in neuronal differentiation or development.

Blood Proteins↗

Intracranial haemorrhage in the preterm sheep fetus.

The germinal layer in the brain of the sheep fetus at 58--85 days of gestation was found to resemble that of the human infant at 28--30 wk of gestation. Experiments were done on 65 exteriorized fetuses to explore the effect of various combinations of asphyxia and raised intravascular pressures in causing bleeding into the germinal layer, ventricles and other parts of the brain. Asphyxia by itself did not produce an increase in the incidence of intracranial hemorrhages when compared with control fetuses. The combination of asphyxia with intermittent increases in arterial or venous pressure, or both, did cause haemorrhages. Large increases in arterial pressure without asphyxia also caused intracranial haemorrhages, whereas increases in venous pressure without asphyxia did not. The types of haemorrhage observed closely resembled those seen in the preterm human infant, although massive intraventricular haemorrhages (IVHs) were rare. We conclude that: (1) the sheep fetus can be used for investigating factors associated with intracranial haemorrhage in the preterm brain; (2) the most effective method of producing haemorrhages into the germinal layer was by a combination of asphyxia with intermittent increases in cerebral intravascular pressure. Similar mechanisms may be at work in the newborn human infant, and could lead to IVH.

Animals↗

Studies of the development of brain barrier systems to lipid insoluble molecules in fetal sheep.

1. The development of the blood-brain and blood-c.s.f barriers to lipid insoluble substances of different molecular radii has been studied in fetal sheep, early (60 days) and late (125 days) in gestation, using labelled erythritol (C14), sucrose (3H or 14C), inulin (3H or 14C) and albumin (125I), or albumin and IgG detected by immunoassay. 2. Morphological studies of fetal brain and choroid plexus at the same gestational stages were carried out using thin section electron microscopy and the freeze fracture techniques. 3. Penetration of markers into c.s.f. was substantially greater at 60 days than at 125 days, but at both ages the steady-state level achieved appeared to be related to molecular size. 4. A simple model describing penetration from blood into c.s.f. at 60 days is proposed. It involves the assumption that c.s.f. and brain extracellular fluid are effectively separate compartments; morphological and permeability data which supports this assumption is presented. The data for c.s.f. at 60 days are consistent with the suggestion that the markers penetrate into c.s.f. by diffusion and are not restricted by small pores in the interface between blood and c.s.f. 5. The reduction in penetration which occurred by 125 days for all markers except erythritol appears to be accounted for by an increase in the sink effect and a decrease in the effective surface area for exchange between blood and c.s.f. 6. Intercellular tight junctions of both cerebral endothelial cells and choroid plexus epithelial cells were well formed at 60 days gestation. There was no change in junctional characteristics previously thought to correlate with transepithelial permeability (tight junction depth and strand number) between the two ages studied, although there were marked changes in permeability. 7. Evidence is advanced in support of the hypothesis that in the fetus much of the penetration of lipid insoluble non-polar substances across the blood-c.s.f. barrier and perhaps across the blood-brain barrier occurs via a transcellular route consisting of a system of tubulo-cisternal endoplasmic reticulum. Penetration via the choroid plexus appears to be the dominant route for penetration from blood into c.s.f. in the 60 day fetus.

Animals↗

Significance of loin pain in women. A study of 100 consecutive cases referred to a urological clinic.

Of 100 consecutive female patients referred to a urology clinic in Sheffield with suspected renal pain, only 22% has upper-urinary-tract lesions. A full history and examination, an analysis of a midstream specimen of urine, and a straight X-ray examination of the renal tract indicated or excluded an upper-urinary-tract lesion in 94% of the cases. In the remaining 6%, where an upper-urinary-tract abnormality was diagnosed only after urography, the findings were incidental in most cases and no treatment was necessary.

Adolescent↗

The effect of local application of vinblastine or cholchinine on acetylcholine accumulation in rat sciatic nerve.

The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentration of colchicine (10(-1), 10(-2 M) and vinblastine (10(-2)-10(-4 M) in a dose-dependent manner. The two mitotic inhibitors were effective both when applied to axons (subepineural injections) and to perikaraya (injections into the lumbar intumescence). The results indicate that mitotic inhibitors, when applied locally to cholinergic motor neurons, may block the proximo-distal transport of ACh. The possibility is discussed that this blockade is caused by an interference with a microtubule mechanism in the axons. Evidence for an increased local synthesis of ACh near the site of injection into nerves also obtained with the highest concentrations of either substance used.

Acetylcholine↗

Effects of colchicine and vinblastine on axonal transport of choline acetyltransferase in rat sciatic nerve.

The effects of colchicine (0.5-10(-2) M) and vinblastine (10(-2)-10(-5) M) Upon axonal transport of choline acetyltranserase (CAT) and on nerve impulse conduction have been investigated in the rat sciatic nerve. High concentrations of colchicine (0.5 M) and vinblastine (10(-2) M) blocked completely both axonal transport of CAT and impulse conduction. 10(-3) M vinblastine did not affect impulse conduction until 20-22 h after injection, but this concentration of vinblastine did block CAT transport but not impulse conduction. 10(-2) M and 10(-1) M colchicine were without effect on impulse conduction, but did produce substantial, although incomplete, block of CAT transport. The results are discussed in relation to the possible involvement of microtubules in transport of CAT.

Acetyltransferases↗

The effect of hypercapnia on a blood-brain barrier mechanism in foetal and new-born sheep.

1. The effect of marked hypercapnia (arterial PCO2 100 mmHg), nonrespiratory acidosis (pH 6-95-7-15) or hypoxia (arterial PO2 10-15 mmHg) upon penetration of labelled sucrose from blood into brain and c.s.f. has been investigated in exteriorized foetal sheep and new-born lambs. 2. In hypercapnia there was a consistent increase in c.s.f./plasma sucrose ratio after 90 min I.V. sucrose to four to five times control. Brain/plasma sucrose ratios were more variable. Usually there was an increase (up to three-and-a-half-times control); sometimes there was no change or even a decrease. The effect of hypercapnia on sucrose penetration was reversible. 3. Hypercapnia reduced c.s.f. secretion rate to approximately half the control value. Hypercapnia also caused a decrease in brain extracellular space. 4. Non-respiratory acidosis did not affect sucrose penetration. Hypoxia caused a decrease in brain/plasma sucrose ratio. 5. It is concluded that hypercapnia can cuase an increase in cerebral vascular permeability to sucrose in foetal and new-born sheep. Some possible mechanisms are discussed.

Acid-Base Equilibrium↗

Complex tight junctions of epithelial and of endothelial cells in early foetal brain.

?The morphology of epithelial and of endothelial intercellular junctions in human foetal (9-15 weeks gestation) and sheep foetal (50, 60 and 125 days gestation, term 147 days) brain has been studied using the freeze-fracture technique and thin section transmission electronmicroscopy. Freeze-fracture replicas of the choroid plexus of both early human and sheep foetuses showed that the choroidal ependymal cells are linked at the ventricular surface by tight junctions. Freeze-fracture replicas of foetal cortical endothelial cell junctions showed that they are still more complex than those of choroidal epithelial cells, in all specimens so far examined. In some 60 day sheep foetuses the dye Alcian blue, which binds to plasma albumin and which iselectrondense when treated with osmium tetroxide, was injected intravenously a few minutes prior to fixation. The dye penetrated from blood into brain extracellular space and c.s.f. but apparently not by an intercellular route. The dye was found in a tubular system (endoplasmic reticulum) in both choroidal epithelial and cortical endothelial cells. The possibility that protein penetrates into the foetal brain and c.s.f. by a transcellular route is discussed. The possible significance of these findings in relation to previous ideas and studies of the development of blood-brain barrier mechanisms is also considered.

Animals↗